Sphingosine 1-Phosphate Receptor Expression Profile in Human Gastric Cancer Cells: Differential Regulation on the Migration and Proliferation1

Yamashita, Hiroharu; Kitayama, Joji; Shida, Dai; Yamaguchi, Hironori; Mori, Ken; Osada, Makoto; Aoki, Shigeji; Yatomi, Yutaka; Takuwa, Yoh; Nagawa, Hirokazu

doi:10.1016/j.jss.2005.08.004

Cited by 76 publications

(76 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these targets, the ability of OSU-A9 and indole-3-carbinol to facilitate Akt dephosphorylation in conjunction with increased phosphorylation of ERKs, JNK, and p38 is mechanistically intriguing. This finding is reminiscent to that reported for a number of molecules, including thrombin (39), sphingosine 1-phosphate (40), and kainate (41), in different cell systems. Moreover, one study with thrombin in human endothelial cells suggests a mechanistic link between the activation of Rho/Rho-kinase signaling and drug-induced divergent effects on the phosphorylation status of Akt and MAP kinases (39), which is currently under investigation in OSU-A9-treated prostate cancer cells.…”

Section: Discussionsupporting

confidence: 84%

A Potent Indole-3-Carbinol–Derived Antitumor Agent with Pleiotropic Effects on Multiple Signaling Pathways in Prostate Cancer Cells

et al. 2007

View full text Add to dashboard Cite

Indole-3-carbinol has emerged as a promising chemopreventive agent due to its in vivo efficacy in various animal models. However, indole-3-carbinol exhibits weak antiproliferative potency and is unstable in acidic milieu. Thus, this study was aimed at exploiting indole-3-carbinol to develop potent antitumor agents with improved chemical stability. This effort culminated in OSU-A9 {[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol}, which is resistant to acid-catalyzed condensation, and exhibits 100-fold higher apoptosis-inducing activity than the parent compound. Relative to indole-3-carbinol, OSU-A9 displays a striking qualitative similarity in its effects on the phosphorylation or expression of multiple signaling targets, including Akt, mitogen-activated protein kinases, Bcl-2 family members, survivin, nuclear factor-KB, cyclin D1, p21, and p27. The ability of OSU-A9 to concurrently modulate this broad range of signaling targets underscores its in vitro and in vivo efficacy in prostate cancer cells. Nevertheless, despite this complex mode of mechanism, normal prostate epithelial cells were less susceptible to the antiproliferative effect of OSU-A9 than PC-3 and LNCaP prostate cancer cells. Treatment of athymic nude mice bearing established s.c. PC-3 xenograft tumors with OSU-A9 at 10 and 25 mg/kg i.p. for 42 days resulted in a 65% and 85%, respectively, suppression of tumor growth. Western blot analysis of representative biomarkers in tumor lysates revealed significant reductions in the intratumoral levels of phosphorylated (p-) Akt, Bcl-xL, and RelA, accompanied by robust increases in p-p38 levels. In conclusion, the ability of OSU-A9 to target multiple aspects of cancer cell survival with high potency suggests its clinical value in prostate cancer therapy. [Cancer Res 2007;67(16):7815-24]

show abstract

Section: Discussionsupporting

confidence: 84%

A Potent Indole-3-Carbinol–Derived Antitumor Agent with Pleiotropic Effects on Multiple Signaling Pathways in Prostate Cancer Cells

et al. 2007

View full text Add to dashboard Cite

show abstract

“…18 We therefore hypothesized that the cytoplasmic location of S1P 1 and/or S1P 3 is a surrogate marker of activation for these receptors in ER-positive breast cancer. The S1P 3 receptor has previously been demonstrated to induce cellular proliferation and have a promigratory effect in a number of cell types, 19,20 including MCF-7 breast cancer cells. 7 This is in line with observations made in the current study, as it is associated with increased tumor size and reduced disease-specific survival.…”

Section: Discussionmentioning

confidence: 99%

High Expression of Sphingosine 1-Phosphate Receptors, S1P1 and S1P3, Sphingosine Kinase 1, and Extracellular Signal-Regulated Kinase-1/2 Is Associated with Development of Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Patients

Watson

Long

Orange

et al. 2010

The American Journal of Pathology

157

155

View full text Add to dashboard Cite

Various studies in cell lines have previously demonstrated that sphingosine kinase 1 (SK1) and extracellular signal-regulated kinase 1/2 (ERK-1/2) interact in an estrogen receptor (ER)-dependent manner to influence both breast cancer cell growth and migration. A cohort of 304 ER-positive breast cancer patients was used to investigate the prognostic significance of sphingosine 1-phosphate (S1P) receptors 1, 2, and 3 (ie, S1P 1 , S1P 2 , and S1P 3 ), SK1, and ERK-1/2 expression levels. Expression levels of both SK1 and ERK-1/2 were already available for the cohort, and S1P 1 , S1P 2 , and S1P 3 levels were established by immunohistochemical analysis. High membrane S1P 1 expression was associated with shorter time to recurrence (P ‫؍‬ 0.008). High cytoplasmic S1P 1 and S1P 3 expression levels were also associated with shorter disease-specific survival times (P ‫؍‬ 0.036 and P ‫؍‬ 0.019, respectively). Those patients with tumors that expressed high levels of both cytoplasmic SK1 and ERK-1/2 had significantly shorter recurrence times than those that expressed low levels of cytoplasmic SK1 and cytoplasmic ERK-1/2 (P ‫؍‬ 0.00008), with a difference in recurrence time of 10.5 years. Similarly, high cytoplasmic S1P 1 and cytoplasmic ERK-1/2 expression levels (P ‫؍‬ 0.004) and high cytoplasmic S1P 3 expression and cytoplasmic ERK-1/2 expression levels (P ‫؍‬ 0.004) were associated with shorter recurrence times. These results support a model in which the interaction between SK1, S1P 1 , and/or S1P 3 and ERK-1/2 might drive breast cancer progression, and these findings, therefore, warrant further investigation.

show abstract

“…The bio-active lipid S1P has been involved in various aspects of tumor development, including cell proliferation, motility and invasiveness, apoptosis, differentiation, angiogenesis and inflammation [28] . However, S1P can mediate both proliferative [29] and antiproliferative [30] effects in neoplastic cells. These opposite responses to S1P were attributed to the different activities exerted by its five receptors, which are coupled to distinct members of the G protein family and display a specific tissue expression pattern [28] .…”

Section: Gpcrs Activated By Bio-active Lipidsmentioning

confidence: 99%

GPCRs and cancer

Lappano

2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.

show abstract

Sphingosine 1-Phosphate Receptor Expression Profile in Human Gastric Cancer Cells: Differential Regulation on the Migration and Proliferation1

Cited by 76 publications

References 41 publications

A Potent Indole-3-Carbinol–Derived Antitumor Agent with Pleiotropic Effects on Multiple Signaling Pathways in Prostate Cancer Cells

A Potent Indole-3-Carbinol–Derived Antitumor Agent with Pleiotropic Effects on Multiple Signaling Pathways in Prostate Cancer Cells

High Expression of Sphingosine 1-Phosphate Receptors, S1P1 and S1P3, Sphingosine Kinase 1, and Extracellular Signal-Regulated Kinase-1/2 Is Associated with Development of Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Patients

GPCRs and cancer

Contact Info

Product

Resources

About